The transferrin receptor gene (cytogenetic location: 3q29) encodes a cell surface receptor required for cellular iron uptake via receptor-mediated endocytosis.
Circulating apotransferrin binds 2 Fe(3+) ions to holotransferrin, which binds to TFRC (Casey et al. 1988). The TFRC-holotransferrin complex is internalized by receptor-mediated endocytosis (see Jabara H H et al. 2016). An important paralog of this gene is TFR2.
The transferrin receptor is required for erythropoiesis and neurological development. Several alternatively spliced variants have been identified.
The transferrin receptor consists of two identical subunits linked by a disulfide bridge. Each monomer has an 85 kD C-terminal component that can bind an iron-loaded transferrin molecule. A small fraction of transferrin receptors detach from the cell surface and can be measured as soluble transferrin receptor in blood.
Related metabolic pathways include vesicle-mediated transport and iron metabolism in the placenta.
A homozygous missense mutation in the TFRC gene (Y20H; 190010.0001) resulted in the clinical picture "immunodeficiency-46" in affected members of a large consanguineous Kuwaiti family (Jabara et al. 2016). The mutation results in increased surface expression of TFRC (up to 13-fold higher than controls) of lymphocytes and impaired internalization of TFRC in affected patients. Evidence suggests that inadequate iron uptake is the cause of impaired B- and T-cell activation in affected individuals. The results support the importance of TFRC for adaptive immunity.